allopurinol and Cytomegalovirus-Infections

Topics: Allopurinol; Ampicillin; Antibody Formation; Cross Reactions; Cytomegalovirus Infections; Drug Contamination; Drug Eruptions; Drug Synergism; Erythema; Humans; Immunity, Cellular; Infectious Mononucleosis; Leukemia, Lymphoid; Lymphocytes; Lymphoma, Large B-Cell, Diffuse; Urticaria

An association between herpes virus reactivations and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is accepted. We report six cases of DRESS with viral reactivation occurring within a single 1-month period. We attempted to find a common factor for these six cases and carried out clinical and virological examinations. Before and after this "epidemic", the mean number of cases of DRESS seen at the same centre was one per quarter, making the occurrence of six cases within a single month all the more remarkable and prompting us to seek an explanation.. All six patients had taken a partly causative medication from different drug classes three to six weeks prior to the start of symptoms and herpes virus was detected in the blood of all of these subjects at the time of DRESS onset (four reactivations and two primary infections), and one patient subsequently displayed herpetic meningoencephalitis 95 days after the initial episode, associated with recurrence of DRESS.. There was no common denominator among these six DRESS patients in terms of either drug class or reactivation of a particular type of herpes virus, which raises the possibility of a single unidentified environmental agent. DRESS does not appear fully explainable in terms of a cellular response to drug antigens but seems rather to result from complex interactions between the drug-induced immune response, viral reactivation and antiviral immune response. Several investigators have reported sequential reactivation of herpes viruses in DRESS. A viral epidemic could thus cause a "DRESS epidemic" in patients on medication.. These cases point to the possible existence of a shared initial environmental factor (infectious or not) that favours reactivation of herpes viruses and induces DRESS in patients on medication. Before and after this "DRESS epidemic", about one patient each quarter was admitted to hospital for DRESS.

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Amoxicillin; Anti-Bacterial Agents; Carbamazepine; Chemical and Drug Induced Liver Injury; Cytomegalovirus; Cytomegalovirus Infections; Disease Outbreaks; Drug Eruptions; Epstein-Barr Virus Infections; Female; France; Herpesvirus 4, Human; Herpesvirus 6, Human; Herpesvirus 7, Human; Humans; Hypereosinophilic Syndrome; Imidazoles; Immunocompromised Host; Male; Middle Aged; Models, Biological; Roseolovirus Infections; Seasons; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Activation

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse cutaneous reactions to drugs. We report here the first case of severe pneumonia caused by an unusual combined infection with Pneumocystis carinii (jiroveci), parainfluenza virus type 3, cytomegalovirus and Aspergillus fumigatus in a 63-year-old female patient with allopurinol-induced SJS/TEN overlap syndrome. Following treatment with high-dose systemic corticosteroids and intravenous immunoglobulin for SJS/TEN, her mucocutaneous lesions improved and she was due to be discharged. However, 15 days after cessation of corticosteroids, she developed pneumonia. Broncho-alveolar lavage revealed that the cause of infection was Pneumocystis carinii (jiroveci), parainfluenza virus type 3, cytomegalovirus and Aspergillus. These findings indicate that patients with SJS/TEN, particularly those treated with systemic corticosteroids, may be susceptible to infection with combinations of pathological agents resulting from damage to the bronchial epithelia.

Topics: Adrenal Cortex Hormones; Allopurinol; Anti-Infective Agents; Aspergillus fumigatus; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Humans; Immunoglobulins, Intravenous; Lung Diseases, Interstitial; Middle Aged; Parainfluenza Virus 3, Human; Pneumocystis carinii; Pneumonia, Pneumocystis; Pulmonary Aspergillosis; Radiography; Respiration, Artificial; Respirovirus Infections; Severity of Illness Index; Stevens-Johnson Syndrome; Treatment Outcome

A 43-year-old man developed fever, skin rash, eosinophillia, and severe renal and liver dysfunction following treatment with allopurinol. The patient died after 3 months of hospitalization. Autopsy revealed systemic cytomegalovirus infection and bacteremia.

Topics: Adult; Allopurinol; Anti-Bacterial Agents; Antiviral Agents; Bacteremia; Cytomegalovirus Infections; Drug Hypersensitivity; Drug Therapy, Combination; Ganciclovir; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Skin; Skin Ulcer

4 wk after intraperitoneal inoculation of 0.2 LD50 (50% lethal dose) of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable in the salivary glands, but not in the lungs or other organs. When the T cells of these mice were activated in vivo by a single injection of anti-CD3 monoclonal antibody, interstitial pneumonitis was induced in the lungs that were free of the virus with an excessive production of the cytokines. In the lungs of such mice persistently infected with MCMV, the mRNA of the cytokines such as IL-2, IL-6, TNF-alpha, and IFN-gamma were abundantly expressed 3 h after the anti-CD3 injection, and the elevated levels continued thereafter. A marked expression of inducible nitric oxide synthetase (iNOS) was then noted in the lungs, suggesting that such cytokines as TNF-alpha and IFN-gamma may have induced iNOS. Although the increase in NO formation was demonstrated by the significant elevation of the serum levels of nitrite and nitrate, the interstitial pneumonitis was not associated with either increased superoxide formation or peroxynitrite-induced tyrosine nitration. Nevertheless, the administration of an NO antagonist also alleviated the interstitial pneumonitis provoked by anti-CD3 mAb. Based on these findings, it was concluded that MCMV-associated pneumonitis is mediated by a molecule of cytokine-induced NO other than peroxynitrite.

Topics: Animals; Antibodies, Monoclonal; Bronchoalveolar Lavage Fluid; CD3 Complex; Cyclic N-Oxides; Cytokines; Cytomegalovirus Infections; Lung; Lung Diseases, Interstitial; Male; Mice; Mice, Inbred BALB C; Muromegalovirus; NG-Nitroarginine Methyl Ester; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Nitrogen Oxides; Polymerase Chain Reaction; Reactive Oxygen Species; RNA, Messenger; Tyrosine; Xanthine Dehydrogenase; Xanthine Oxidase

Topics: Adult; Allopurinol; Cytomegalovirus Infections; Herpes Simplex; Humans; Kidney Transplantation; Male; Tumor Virus Infections; Virus Diseases